Question
What constitutes a sulfa allergy?
Response from Lauren R. Cirrincione, PharmD Postdoctoral Research Associate, Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, Nebraska |
|
Response from Kimberly K. Scarsi, PharmD Associate Professor, Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, Nebraska |
A chart review of 2.4 million patients in California found that approximately 4% reported an allergy to sulfonamide antimicrobials.[1] The term "sulfonamide antimicrobial" includes trimethoprim/sulfamethoxazole (TMP/SMX), sulfadiazine, and erythromycin/sulfisoxazole.[2] Sulfonamide antimicrobials differ in chemical structure from nonantimicrobial sulfonamides, and those structural differences are implicated in hypersensitivity associated with sulfa antimicrobials.[3,4,5,6]
Drug allergy, broadly called "hypersensitivity," is an immune-mediated response against a medication.[7] Hypersensitivity reactions may present either immediately (within 1 hour) or be delayed (between 1 and 48 hours).[4,8] Immediate hypersensitivity is generally immunoglobulin E (IgE)-mediated urticaria, angioedema, rhinitis, bronchospasm, or anaphylaxis. Delayed hypersensitivity is T-cell dependent, presenting as either a maculopapular rash or more serious blistering and mucosal involvement, presaging Stevens-Johnson syndrome or toxic epidermal necrolysis.[7]
Sulfonamide antimicrobial hypersensitivity is predominantly T-cell mediated, presenting as delayed cutaneous reactions, such as a pruritic maculopapular rash,that occurs 1-2 weeks after exposure.[3,7,9] IgE-mediated allergic responses have been reported[3,5,6]; however, immediate hypersensitivity is less common.[7]
Skin involvement is the hallmark of most drug allergies. A study of 94 patients found that 63% of reported TMP/SMX allergies were rash and hives.[10] Sulfonamide-induced rashes usually start at the trunk and spread toward the limbs[7] and generally resolve within 2 weeks after discontinuation of the medication.[3,4,5] If mucosal membranes are involved or blistering is present, the patient may require hospitalization.[7] More severe cases can present as a syndrome, including fever and organ damage, in addition to a generalized maculopapular rash.[3,4] Rarely, sulfonamide antimicrobials have been associated with toxic epidermal necrolysis and Stevens-Johnson syndrome.[4]
The American Academy of Allergy, Asthma, and Immunology (AAAAI) has guidance on assessing and managing drug hypersensitivity reactions. This resource provides step-by-step instruction on identifying and managing medication allergies, including an algorithm for patient care during a suspected drug allergy.
Patient-specific risk factors include a history of other drug allergies and previous use of the suspected medication or medication class. Females are reported to have more reported drug hypersensitivity,[1,7] and individuals with comorbidities, such as HIV infection and systemic lupus erythematosus, also are known to be more susceptible to drug hypersensitivity.[7]
Drug-specific factors, including duration of exposure and dose, should be considered to differentiate drug toxicities from drug allergies.[7] If a drug allergy is suspected, a detailed review of the patient's current medications, including nonprescription medicines and supplements, is critical, because this may help determine whether a sulfonamide agent is solely responsible for symptoms.[7]
A variety of desensitization protocols are available,[11] but implementing such a protocol should be delayed for 1 month after symptoms have resolved. And although these desensitization protocols have been evaluated,[3] their results are limited to patients with HIV owing to the use of TMP/SMX prophylaxis.[11]
Cross-reactivity with nonantimicrobial sulfonamides is a theoretical consideration for patients with a reported "sulfa allergy." Commonly prescribed nonantimicrobial sulfonamides include furosemide, hydrochlorothiazide, acetazolamide, sulfonylureas, and celecoxib.[10,12] Clinically significant cross-reactivity between antimicrobial and nonantimicrobial sulfonamides is not a concern.[10] A retrospective cohort study of 969 patients with reported sulfa allergy concluded that there were no clinically significant allergic responses in patients with a documented sulfonamide allergy to subsequently administered nonantimicrobial sulfonamides.[12] Currently, the AAAAI concludes that there is no evidence to support cross-reactivity with nonantimicrobial sulfonamides in patients with reported allergy to antimicrobial sulfonamides.[7]
Sulfites are found in processed foods[5,13,14] and medication preparations,[13] and they can trigger asthma exacerbations in patients with a history of asthma.[10,13,14] Sulfites are chemically different from sulfonamides, so this reaction is unrelated to sulfonamide hypersensitivity.[10] There is no risk for cross-sensitivity between antimicrobial sulfonamides and sulfur-containing compounds, such as sulfites.[5,10]
Sulfur and sulfate are found naturally in the body; sulfa-containing amino acids (eg, cysteine) and sulfate-containing drugs (eg, ferrous sulfate) and dietary supplements (eg, glucosamine sulfate) are not allergenic in patients with antimicrobial sulfonamide hypersensitivity.[15] In contrast, topical sulfonamides, such as silver sulfadiazine and ophthalmic sulfacetamide/prednisolone, are contraindicated in patients with documented sulfonamide allergy.[14,16,17] One small study (5 participants) reported cross-reactivity with sulfasalazine and antimicrobial sulfonamides owing to similarities in chemical structures.[9]
In conclusion:
The onset and types of symptoms, as well evaluation of pertinent patient data—including previous exposure to an offending mediation—can guide in the differential diagnosis of an allergic reaction to a suspected agent.
Sulfonamide hypersensitivity reactions frequently present as a maculopapular rash that resolves approximately 2 weeks after discontinuation of the sulfonamide.
Clinicians should be aware of signs of potentially serious delayed reactions, including blistering and involvement of mucosal membranes.
Cross-reactive hypersensitivity between sulfonamide antimicrobials and nonantimicrobials is unlikely.
Cross-sensitivity with sulfur-containing compounds, such as sulfites, and sulfonamide antimicrobials does not occur.
Sulfur and sulfate-containing drugs are not allergenic in patients with antimicrobial sulfonamide hypersensitivity.
Topical sulfonamide antimicrobials are contraindicated in patients with sulfonamide hypersensitivity.
Editors' Recommendations |
Medscape Pharmacists © 2016 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Sulfa, Sulfur, Sulfate, Sulfite: Which Causes an Allergy? - Medscape - Oct 19, 2016.
Comments